Classifications

• • B—PERFORMING OPERATIONS; TRANSPORTING
  • B82—NANOTECHNOLOGY
  • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
  • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
  • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
  • A61K47/40—Cyclodextrins; Derivatives thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
  • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
  • A61K47/6949—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
  • A61K47/6951—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner

Definitions

• CDEX 2-hydroxypropyl- ⁇ -cyclodextrin
• This invention concerns the use of 2-hydroxypropyl- ⁇ -cyclo- dextrin (CDEX) for preparing an opioid preparation for intramuscular or subcutaneous administration having a sustained systemic pain alleviating effect.
• CDEX 2-hydroxypropyl- ⁇ -cyclo- dextrin
• CDEX 2-Hydroxypropyl- ⁇ -cyclodextrin
• the inclusion complex formation will alter the physicochemical properties of the test drug, for example increase the water solubility since the drug/CDEX complex adapts the solubility of CDEX. Furthermore the pharmacokine- tics of the drug can be altered since the free amount available for clearance or biological interactions is dependent on mass action kinetics, showing a time dependent dissociation into the surrounding biophase.
• CDEX has been studied thoroughly with a view to finding a solubilizing agent for lipid- soluble drugs.
• the studies have shown that CDEX is an outstanding solubilizing agent having clear advantages to the previously used agents such as propylene glycol, fat emulsions, cremophor etc.
• CDEX has been used in combination with a variety of lipid medicaments, i.a. antihypertensive agents, hormone drugs and agents for starting systemic anaesthesia (1, 2, 5, 13, 14, 15). All these lipid-soluble medicaments are water-soluble in combination with CDEX and, therefore, can be used for injection in humans. Decisive for the use of CDEX in such combinations is its systemic and local toxicity.
• opioid analgesics e.g. morphine, ketobemidone, nicomorphine and meperidine
• opioid analgesics e.g. morphine, ketobemidone, nicomorphine and meperidine
• an opioid is injected im. or sc. it has to be absorbed into the blood ⁇ stream, transported to the brain, pass the blood-brain barrier and eventually reach the opioid receptors in the brain in order to exert its analgesic effect. Thereby the effect is systemic.
• Numerous studies have shown that the agents are used insufficiently, in particular due to too low doses and too long time intervals between the dosages.
• Opioids are also used in quite another way, namely by intra- thecal injection (i.e. injection into the fluid surrounding the spinal cord) in order to achieve a localized analgesic effect at certain spinal nerve segments.
• the European Patent Application 430 414 Al describes a morphine hydrochloride preparation for rectal administra- tion. It is a filled hollow type suppository for rectal administration containing a mixture of morphine hydrochlo ⁇ ride with one or more cyclodextrins, i.a. hydroxypropyl- ⁇ - cyclodextrin, and it is said to be markedly improved in bioavailability and stability compared to morphine supposi- tories of the prior art.
• the present invention comprises the use of CDEX for preparing an opioid analgesic preparation for intramu- scular or subcutaneous administration, said preparation having a sustained systemic pain alleviating effect.
• the Opioids are usually used as analgesics in aqueous solutions having concentrations of opioid of from 0.01 to 2.0 % weight/vol.
• concentrations of opioid of from 0.01 to 2.0 % weight/vol.
• the maximum concentration of morphine is 3.5 % weight/vol.
• concentration of opioid 0.01-4.0 % weight/vol.
• the optimal concentration of CDEX in a preparation containing 1 % weight/vol. of morphine is 0.2 % weight/vol. It is thus conceivable that good results can be achieved with preparations made by use of the inven- tion, in which the amount of CDEX is 5-100 %, preferably 10- 50 %, and more preferably about 20 % by weight of the opioid.
• the prolongation of morphine's effect following im. or sc. injection in combination with CDEX is mainly due to a more physiological release from the injection site, i.e. a lower initial peak plasma concentration.
• the combination of CDEX and morphine in the optimal concentrations results in an unaltered maximum effect and an increase in the duration of action of more than 80 %.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Engineering & Computer Science (AREA)
• Pharmacology & Pharmacy (AREA)
• Medicinal Chemistry (AREA)
• Veterinary Medicine (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Epidemiology (AREA)
• Nanotechnology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biophysics (AREA)
• Crystallography & Structural Chemistry (AREA)
• Dermatology (AREA)
• Molecular Biology (AREA)
• Medical Informatics (AREA)
• General Engineering & Computer Science (AREA)
• Biotechnology (AREA)
• Inorganic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Citations (3)

• 1993
  • 1993-08-17 DK DK93939A patent/DK93993D0/da not_active Application Discontinuation
• 1994
  • 1994-08-16 AU AU73830/94A patent/AU7383094A/en not_active Abandoned
  • 1994-08-16 WO PCT/DK1994/000306 patent/WO1995005197A1/en not_active Ceased

Patent Citations (3)

Non-Patent Citations (3)

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